The Lysosomal Disease GRC had its first meeting at the Hotel Galvez in Galveston, Texas in 2011, and its second at the Renaissance Tuscany Il Ciocco Resort in Lucca (Barga), Italy in 2013. We are one of the newest of over 170 annual conferences organized by the GRC, an organization known world-wide for its high-quality, cutting-edge academic conferences, and indeed are the only new GRC approved as a repeat conference in their 2013 review. Lysosomal Disease represents a group of more than 50 disorders caused by inherited defects in a wide spectrum of proteins, many of which remain poorly understood. These disorders affect many organ systems, most notably brain, leading to chronic illness and death of affected individuals. The 2015 Lysosomal Disease GRC will again offer a critical venue for addressing major challenges involving lysosomal diseases, including the need for better understanding of (1) the role of the greater lysosomal system in maintaining cell homeostasis in health and disease, (2) lysosomal disease pathogenic mechanisms underlying the dysfunction of neurons and brain, as well as other cell types/organs/systems, (3) specific functions of lysosomal and non-lysosomal proteins, defects in which cause lysosomal disease, (4) the relationship between lysosomal dysfunction and other chronic neurodegenerative conditions (e.g., Alzheimer's and Parkinson's), and (5) the extent to which heterozygosity in autosomal and X-linked lysosomal diseases can lead to cellular and clinical disease. Additionally there is the challenge (6) through rigorous preclinical studies to develop new and innovative therapies for these disorders coupled with (7) initiating and completing effective clinical trials. To address these important topics we have to date invited, as speakers and discussants, 27 leading and internationally known scientists and clinicians working in the field of lysosomal disease. Each has accepted our invitation and will join what we anticipate to be an additional 170 attendees; fully one-third of whom we anticipate will be junior investigators, postdoctoral fellows and graduate students who are at the early stages of their careers. Importantly, the success of our 2011 meeting led to the GRC Organization selecting the Lysosomal Disease meeting as a host for a Gordon Research Seminar (GRS), a special meeting organized and run by graduate students and early postdoctoral fellows. Our 2015 meeting has again been selected to host a GRS. The presence of the GRS insures that the very best and the brightest of the next generation of lysosomal disease researchers will be part of the GRC as well. The discussion and cross fertilization of ideas and approaches occurring as part of the GRC and GRS meetings we believe will accelerate not only our understanding of the role of the lysosomal system in health and in disease, but also move us closer to effective therapies for many of these disorders.